ES2621458T3 - RSV specific binding molecule - Google Patents
RSV specific binding molecule Download PDFInfo
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- ES2621458T3 ES2621458T3 ES09788359.9T ES09788359T ES2621458T3 ES 2621458 T3 ES2621458 T3 ES 2621458T3 ES 09788359 T ES09788359 T ES 09788359T ES 2621458 T3 ES2621458 T3 ES 2621458T3
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- 230000009870 specific binding Effects 0.000 title 1
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 abstract description 5
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 abstract description 4
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 abstract description 4
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 abstract description 4
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 abstract description 3
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 abstract 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 abstract 1
- 241000700605 Viruses Species 0.000 abstract 1
- 230000000241 respiratory effect Effects 0.000 abstract 1
- 208000011580 syndromic disease Diseases 0.000 abstract 1
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- 238000000034 method Methods 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 2
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
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- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- 101150050927 Fcgrt gene Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
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- 241000124008 Mammalia Species 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
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- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1027—Paramyxoviridae, e.g. respiratory syncytial virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/32—Immunoglobulins specific features characterized by aspects of specificity or valency specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- Genetics & Genomics (AREA)
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Abstract
Un anticuerpo aislado, sintético o recombinante o una parte funcional del mismo, caracterizado porque es capaz de enlazar o unirse específicamente a la proteína F del Virus Respiratorio Sincicial (RSV) y el cual comprende: - una secuencia de la región determinante de la complementariedad (CDR) 1 de cadena pesada que comprende la secuencia KLSIH, - una secuencia CDR2 de cadena pesada que comprende la secuencia GYEGEVDEIFYAQKFQH, - una secuencia CDR3 de cadena pesada que comprende la secuencia LGVTVTEAGLGIDDY, - una secuencia CDR1 de cadena ligera que comprende la secuencia RASQIVSRNHLA, - una secuencia CDR2 de cadena ligera que comprende la secuencia GASSRAT, y - una secuencia CDR3 de cadena ligera que comprende la secuencia LSSDSSI.An isolated, synthetic or recombinant antibody or a functional part thereof, characterized in that it is capable of specifically binding or binding to the Syndrome of Respiratory Virus (RSV) F protein and which comprises: - a sequence of the complementarity determining region ( CDR) 1 heavy chain comprising the KLSIH sequence, - a heavy chain CDR2 sequence comprising the GYEGEVDEIFYAQKFQH sequence, - a heavy chain CDR3 sequence comprising the LGVTVTEAGLGIDDY sequence, - a light chain CDR1 sequence comprising the RASQIVSRNHLA sequence , - a light chain CDR2 sequence comprising the GASSRAT sequence, and - a light chain CDR3 sequence comprising the LSSDSSI sequence.
Description
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-una secuencia CDR3 de cadena ligera que comprende la secuencia LSSDSSI. - a light chain CDR3 sequence comprising the LSSDSSI sequence.
En la presente también se describe un anticuerpo aislado, sintético o recombinante o una parte funcional, derivado y/o análogo del mismo el cual es capaz de unirse específicamente a un epítopo que es reconocido por un anticuerpo AM22 el cual comprende: Also described herein is an isolated, synthetic or recombinant antibody or a functional, derivative and / or analogous part thereof which is capable of specifically binding to an epitope that is recognized by an AM22 antibody which comprises:
-una secuencia CDR1 de cadena pesada que comprende la secuencia KLSIH, y - a heavy chain CDR1 sequence comprising the KLSIH sequence, and
-una secuencia CDR2 de cadena pesada que comprende la secuencia GYEGEVDEIFYAQKFQH, y - a heavy chain CDR2 sequence comprising the sequence GYEGEVDEIFYAQKFQH, and
-una secuencia CDR3 de cadena pesada que comprende la secuencia LGVTVTEAGLGIDDY, y - a heavy chain CDR3 sequence comprising the LGVTVTEAGLGIDDY sequence, and
-una secuencia CDR1 de cadena ligera que comprende la secuencia RASQIVSRNHLA, y - a light chain CDR1 sequence comprising the RASQIVSRNHLA sequence, and
-una secuencia CDR2 de cadena ligera que comprende la secuencia GASSRAT, y - a light chain CDR2 sequence comprising the GASSRAT sequence, and
-una secuencia CDR3 de cadena ligera que comprende la secuencia LSSDSSI. - a light chain CDR3 sequence comprising the LSSDSSI sequence.
Ciertas modificaciones de la región constante (Fc) del anticuerpo pueden alterar las funciones realizadoras. Por ejemplo, se incrementa la vida media del suero de proteínas que comprende regiones Fc al incrementar la afinidad de unión de la región Fc para FcRn. El término "vida media del anticuerpo" que se utiliza en la presente significa una propiedad farmacocinética de un anticuerpo que es una medida del tiempo de supervivencia medio de las moléculas del anticuerpo después de su administración. La vida media del anticuerpo se puede expresar como el tiempo requerido para eliminar el 50 por ciento de una cantidad conocida de inmunoglobulina del cuerpo del paciente (u otro mamífero) o un compartimento específico del mismo, por ejemplo, que se mide en el suero, es decir, la vida media circulante, o en otros tejidos. La vida media puede variar de una inmunoglobulina o clase de inmunoglobulina a otra. En general, un incremento en la vida media del anticuerpo da como resultado un incremento en el tiempo de residencia medio (MRT) en circulación para el anticuerpo administrado. El incremento en la vida media permite la reducción en la cantidad del fármaco dado a un paciente así como la reducción de la frecuencia de administración. Para incrementar la vida media del suero de un anticuerpo de acuerdo a la invención, se puede incorporar un epítopo de unión del receptor de rescate en el anticuerpo (especialmente un fragmento de anticuerpo) como se describe en la Patente Norteamericana No. 5,739,277, por ejemplo. Cuando se utiliza en la presente, el término "epítopo de unión del receptor de rescate" se refiere a un epítopo de la región Fc de una molécula IgG (por ejemplo, IgG1, IgG2, IgG3, o IgG4) que es responsable de incrementar la vida media del suero in vivo de la molécula IgG. Alternativamente, los anticuerpos de la invención con vidas medias incrementadas pueden generarse modificando los residuos de aminoácidos identificados como involucrados en la interacción entre el Fc y un receptor FcRn (ver, por ejemplo, las Patentes Norteamericanas Nos. 6,821,505 y 7,083,784). Además, la vida media de los anticuerpos de la invención puede incrementarse mediante la conjugación al PEG o Albúmina mediante técnicas ampliamente utilizadas en el arte. En algunas modalidades los anticuerpos que comprenden las regiones variantes Fc de la invención tienen una vida media incrementada de aproximadamente 5 %, aproximadamente 10 %, aproximadamente 15 %, aproximadamente 20 %, aproximadamente 25 %, aproximadamente 30 %, aproximadamente 35 %, aproximadamente 40 %, aproximadamente 45 %, aproximadamente 50 %, aproximadamente 60 %, aproximadamente 65 %, aproximadamente 70 %, aproximadamente 80 %, aproximadamente 85 %, aproximadamente 90 %, aproximadamente 95 %, aproximadamente 100 %, aproximadamente 125 %, aproximadamente 150 % o más en comparación con un anticuerpo que comprende una región Fc natural. En algunas modalidades los anticuerpos que comprenden regiones de la variante Fc tienen una vida media incrementada aproximadamente 2 veces, aproximadamente 3 veces, aproximadamente 4 veces, aproximadamente 5 veces, aproximadamente 10 veces, aproximadamente 20 veces, aproximadamente 50 veces o más, o está entre 2 veces y 10 veces, o entre 5 veces y 25 veces, o entre 15 veces y 50 veces, en comparación con un anticuerpo que comprende una región Fc natural. La divulgación por lo tanto proporciona un anticuerpo o parte funcional de acuerdo a la invención, que comprende un epítopo de unión del receptor de rescate, y/o residuos aminoácidos modificados identificados como involucrados en la interacción entre el Fc y un receptor FcRN, y/o residuos de aminoácidos que no se presentan de manera natural. Otra modalidad preferida proporciona un anticuerpo Certain modifications of the constant region (Fc) of the antibody may alter the performance functions. For example, the half-life of the protein whey comprising Fc regions is increased by increasing the binding affinity of the Fc region for FcRn. The term "antibody half-life" used herein means a pharmacokinetic property of an antibody that is a measure of the average survival time of the antibody molecules after administration. The half-life of the antibody can be expressed as the time required to remove 50 percent of a known amount of immunoglobulin from the patient's body (or other mammal) or a specific compartment thereof, for example, which is measured in the serum, that is, the circulating half-life, or in other tissues. The half-life may vary from one immunoglobulin or immunoglobulin class to another. In general, an increase in the half-life of the antibody results in an increase in the average residence time (MRT) in circulation for the administered antibody. The increase in the half-life allows the reduction in the amount of the drug given to a patient as well as the reduction of the frequency of administration. To increase the serum half-life of an antibody according to the invention, a rescue receptor binding epitope can be incorporated into the antibody (especially an antibody fragment) as described in US Patent No. 5,739,277, for example . When used herein, the term "rescue receptor binding epitope" refers to an epitope of the Fc region of an IgG molecule (eg, IgG1, IgG2, IgG3, or IgG4) that is responsible for increasing the In vivo serum half-life of the IgG molecule. Alternatively, the antibodies of the invention with increased half-lives can be generated by modifying the amino acid residues identified as being involved in the interaction between the Fc and an FcRn receptor (see, for example, US Pat. Nos. 6,821,505 and 7,083,784). In addition, the half-life of the antibodies of the invention can be increased by conjugation to PEG or Albumin by techniques widely used in the art. In some embodiments the antibodies comprising the Fc variant regions of the invention have an increased half-life of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40 %, approximately 45%, approximately 50%, approximately 60%, approximately 65%, approximately 70%, approximately 80%, approximately 85%, approximately 90%, approximately 95%, approximately 100%, approximately 125%, approximately 150% or more in comparison to an antibody comprising a natural Fc region. In some embodiments, antibodies comprising regions of the Fc variant have an increased half-life approximately 2 times, approximately 3 times, approximately 4 times, approximately 5 times, approximately 10 times, approximately 20 times, approximately 50 times or more, or are between 2 times and 10 times, or between 5 times and 25 times, or between 15 times and 50 times, compared to an antibody comprising a natural Fc region. The disclosure therefore provides an antibody or functional part according to the invention, comprising a rescue receptor binding epitope, and / or modified amino acid residues identified as being involved in the interaction between the Fc and an FcRN receptor, and / or amino acid residues that do not occur naturally. Another preferred embodiment provides an antibody
o equivalente funcional de acuerdo a la invención el cual se conjuga al PEG o Albúmina. or functional equivalent according to the invention which is conjugated to PEG or Albumin.
En una modalidad, la presente divulgación proporciona variantes Fc de acuerdo a la invención, en donde la región Fc comprende una modificación (por ejemplo, sustitución de aminoácidos, inserción de aminoácidos, eliminación de aminoácidos) en una o más posiciones seleccionadas del grupo que consiste en 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 247, 251, 252, 254, 255, 256, 262, 263, 264, 265, y 443, tal como se numeran por el índice EU como se establece en Kabat et al (J Immunol. 1991; 147 (5):1709-19). Opcionalmente, la región Fc comprende un residuo de aminoácido no presente de manera natural en posiciones adicionales y/o alternativas conocidas para un experto en la técnica (ver, por ejemplo, las Patentes Norteamericanas Nos. 5,624,821; 6,277,375; 6,737,056; 7,083,784; 7,317,091; 7,217,797; 7,276,585; 7,355,008; 2002/0147311; 2004/0002587; 2005/0215768; 2007/0135620; 2007/0224188; 2008/0089892; WO 94/29351; y WO 99/58572). In one embodiment, the present disclosure provides Fc variants according to the invention, wherein the Fc region comprises a modification (for example, amino acid substitution, amino acid insertion, amino acid elimination) at one or more positions selected from the group consisting in 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 247, 251, 252, 254, 255, 256, 262, 263, 264, 265, and 443, as numbered by the EU index as stated in Kabat et al (J Immunol. 1991; 147 (5): 1709-19). Optionally, the Fc region comprises an amino acid residue not naturally present in additional positions and / or alternatives known to one skilled in the art (see, for example, US Pat. Nos. 5,624,821; 6,277,375; 6,737,056; 7,083,784; 7,317,091; 7,217,797; 7,276,585; 7,355,008; 2002/0147311; 2004/0002587; 2005/0215768; 2007/0135620; 2007/0224188; 2008/0089892; WO 94/29351; and WO 99/58572).
En una modalidad específica, la presente divulgación proporciona un anticuerpo de la variante Fc de acuerdo a la invención, en donde la región Fc comprende al menos un aminoácido no presente de manera natural en una o más posiciones seleccionadas del grupo que consiste en 252, 254 y 256. En una modalidad, los aminoácidos no presentes de manera natural se seleccionan del grupo que consiste en 252Y, 254T y 256E. In a specific embodiment, the present disclosure provides an antibody of the Fc variant according to the invention, wherein the Fc region comprises at least one amino acid not naturally present in one or more positions selected from the group consisting of 252, 254 and 256. In one embodiment, amino acids not naturally present are selected from the group consisting of 252Y, 254T and 256E.
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productoras preferiblemente esté libre de agentes patógenos tales como microrganismos patógenos. Más preferiblemente, se generan anticuerpos o equivalentes funcionales que consisten de secuencias humanas utilizando al menos una secuencia de ácido nucleico o vector de acuerdo a la invención. Producers preferably be free of pathogens such as pathogenic microorganisms. More preferably, antibodies or functional equivalents are generated consisting of human sequences using at least one nucleic acid sequence or vector according to the invention.
Por lo tanto también se proporciona un anticuerpo aislado o recombinante que produce células capaces de producir un anticuerpo o una parte funcional, derivado y/o análogo del mismo de acuerdo a la invención, así como un método para producir un anticuerpo aislado, sintético o recombinante o parte funcional, derivado y/o análogo de acuerdo a la invención, que comprende proporcionar una célula con una secuencia de ácido nucleico o equivalente funcional o vector de acuerdo a la invención y permitir trasladar dicha célula a dicha secuencia de ácido nucleico o equivalente funcional o vector, produciendo así dicho anticuerpo o parte funcional, derivado y/o análogo del mismo. Therefore, an isolated or recombinant antibody is also provided which produces cells capable of producing an antibody or a functional part, derivative and / or analog thereof according to the invention, as well as a method for producing an isolated, synthetic or recombinant antibody. or functional part, derivative and / or analog according to the invention, which comprises providing a cell with a nucleic acid sequence or functional equivalent or vector according to the invention and allowing said cell to be transferred to said nucleic acid sequence or functional equivalent. or vector, thereby producing said antibody or functional part, derivative and / or analog thereof.
Un anticuerpo que produce la célula se define en la presente como una célula la cual es capaz de producir y/o secretar un anticuerpo o un equivalente funcional del mismo, y/o el cual es capaz de desarrollarse en una célula la cual es capaz de producir y/o secretar un anticuerpo o un equivalente funcional del mismo. Un anticuerpo que produce la célula de acuerdo a la invención preferiblemente es una célula productora la cual se adapta a la producción de anticuerpos comerciales. Preferiblemente, dicha célula productora es adecuada para producir anticuerpos para usarse en humanos. An antibody that the cell produces is defined herein as a cell which is capable of producing and / or secreting an antibody or a functional equivalent thereof, and / or which is capable of developing in a cell which is capable of produce and / or secrete an antibody or a functional equivalent thereof. An antibody that produces the cell according to the invention is preferably a producing cell which adapts to the production of commercial antibodies. Preferably, said producer cell is suitable for producing antibodies for use in humans.
Un método de acuerdo a la invención preferiblemente comprende además una etapa para cosechar, purificar y/o aislar dicho anticuerpo o parte funcional, derivado y/o análogo del mismo de acuerdo a la invención. Los anticuerpos o equivalentes funcionales obtenidos de acuerdo a la invención preferiblemente se utilizan en terapia humana, opcionalmente después de las etapas adicionales de purificación, aislamiento o procesamiento. A method according to the invention preferably further comprises a step for harvesting, purifying and / or isolating said antibody or functional part, derivative and / or analog thereof according to the invention. The antibodies or functional equivalents obtained according to the invention are preferably used in human therapy, optionally after the additional steps of purification, isolation or processing.
Ahora que se han provisto por lo tanto anticuerpos o equivalentes funcionales mejorados específicos al Virus Respiratorio Sincicial de acuerdo a la invención y las secuencias de ácido nucleico y vectores de codificación, incluyendo los anticuerpos humanos o equivalentes funcionales, se han vuelto disponibles aplicaciones profilácticas y/o terapéuticas mejoradas. El RSV es contrarrestado por los anticuerpos o equivalentes funcionales de acuerdo a la invención. Un anticuerpo o equivalente funcional de acuerdo a la invención por lo tanto es particularmente adecuado para usarse como una medicina o agente profiláctico, opcionalmente en combinación con al menos otro anticuerpo específico al RSV conocido en la técnica. Preferiblemente, se utilizan anticuerpos o equivalentes funcionales los cuales consisten en secuencias humanas, o los cuales contienen como máximo un 5 % de secuencias no humanas, a fin de reducir la probabilidad de efectos secundarios adversos cuando se tratan individuos humanos. Un anticuerpo aislado, sintético o recombinante o una parte funcional, derivado y/o análogo del mismo o una secuencia de ácido nucleico o equivalente funcional de la misma o un vector o una célula de acuerdo a la invención para usarse como un medicamento y/o agente profiláctico por lo tanto también se proporciona con el mismo. Cuando se administra un ácido nucleico o equivalente funcional o vector de acuerdo a la invención, se trasladará in situ en un anticuerpo o equivalente funcional de acuerdo a la invención. En una modalidad particularmente preferida dicho anticuerpo comprende el anticuerpo AM22, o un equivalente funcional del mismo. Dicho medicamento o agente profiláctico preferiblemente se utiliza para contrarrestar o al menos en parte prevenir una infección por RSV. Además se proporciona por lo tanto un anticuerpo aislado, sintético o recombinante o una parte funcional, derivado y/o análogo del mismo o una secuencia de ácido nucleico o equivalente funcional de la misma o vector o célula de acuerdo a la invención para usarse como un medicamento y/o agente profiláctico para al menos en parte tratar y/o prevenir un padecimiento relacionado al RSV. Un medicamento que comprende AM22 en combinación con al menos otro agente específico al RSV, preferiblemente un anticuerpo, conocido en la técnica, es particularmente ventajoso debido a que con tal combinación se obtiene una respuesta inmunógena más fuerte al RSV y/o se alcanza una mayor especificidad del anticuerpo contra el RSV. Además se proporciona por lo tanto una combinación de un anticuerpo aislado, sintético o recombinante o una parte funcional, derivado y/o análogo del mismo o una secuencia de ácido nucleico o equivalente funcional del mismo o vector o célula de acuerdo a la invención y otro agente específico al RSV diferente, preferiblemente un anticuerpo o equivalente funcional del mismo, para usarse como un medicamento y/o agente profiláctico. Una combinación de acuerdo a la invención preferiblemente comprende el AM22 y un anticuerpo seleccionado del grupo que consiste en palivizumab, D25, AM14, AM16 y AM23. Como se menciona anteriormente, tal combinación es particularmente adecuada para al menos en parte tratar o prevenir un padecimiento relacionado con el RSV. Además se proporciona por lo tanto un uso de una combinación de acuerdo a la invención para la preparación de un medicamento y/o agente profiláctico al menos en parte para tratar y/o prevenir un padecimiento relacionado al RSV. Por lo tanto también se proporciona un uso de un anticuerpo aislado, sintético o recombinante o una parte funcional, derivado y/o análogo del mismo o una secuencia de ácido nucleico o equivalente funcional del mismo o vector o célula de acuerdo a la invención para la preparación de un medicamento y/o agente profiláctico para al menos en parte tratar y/o prevenir un padecimiento relacionado con el RSV, así como un método para al menos en parte tratar o prevenir un padecimiento relacionado con el RSV, el método comprende administrar a un individuo en necesidad del mismo una cantidad terapéuticamente efectiva de un anticuerpo aislado, sintético o recombinante o una parte funcional, derivado y/o análogo del mismo de acuerdo a la invención. En una modalidad preferida, se utiliza una combinación con al menos otro agente específico al RSV, preferiblemente otro anticuerpo específico del RSV. Dicho individuo preferiblemente ha sido diagnosticado como infectado por RSV antes del tratamiento. Now that antibodies or enhanced functional equivalents specific to the Respiratory Syncytial Virus according to the invention have therefore been provided and the nucleic acid sequences and coding vectors, including the human antibodies or functional equivalents, prophylactic applications and / or or improved therapeutics. RSV is counteracted by antibodies or functional equivalents according to the invention. An antibody or functional equivalent according to the invention is therefore particularly suitable for use as a medicine or prophylactic agent, optionally in combination with at least one other RSV specific antibody known in the art. Preferably, antibodies or functional equivalents are used which consist of human sequences, or which contain a maximum of 5% of non-human sequences, in order to reduce the likelihood of adverse side effects when treating human individuals. An isolated, synthetic or recombinant antibody or a functional, derivative and / or analogous part thereof or a nucleic acid sequence or functional equivalent thereof or a vector or a cell according to the invention for use as a medicament and / or Prophylactic agent is therefore also provided with it. When a functional nucleic acid or equivalent or vector according to the invention is administered, it will be translated in situ into an antibody or functional equivalent according to the invention. In a particularly preferred embodiment said antibody comprises the AM22 antibody, or a functional equivalent thereof. Said medicament or prophylactic agent is preferably used to counteract or at least partly prevent an RSV infection. In addition, there is therefore provided an isolated, synthetic or recombinant antibody or a functional, derivative and / or analogous part thereof or a nucleic acid sequence or functional equivalent thereof or vector or cell according to the invention for use as a medication and / or prophylactic agent to at least partly treat and / or prevent a condition related to RSV. A medicament comprising AM22 in combination with at least one other RSV-specific agent, preferably an antibody, known in the art, is particularly advantageous because with such a combination a stronger immunogenic response to RSV is obtained and / or a greater specificity of the antibody against RSV. Furthermore, a combination of an isolated, synthetic or recombinant antibody or a functional, derivative and / or analogous part thereof or a nucleic acid sequence or functional equivalent thereof or vector or cell according to the invention and other is also provided. specific RSV specific agent, preferably an antibody or functional equivalent thereof, for use as a medicament and / or prophylactic agent. A combination according to the invention preferably comprises AM22 and an antibody selected from the group consisting of palivizumab, D25, AM14, AM16 and AM23. As mentioned above, such a combination is particularly suitable for at least in part treating or preventing a condition related to RSV. In addition, a use of a combination according to the invention is therefore provided for the preparation of a medicament and / or prophylactic agent at least in part to treat and / or prevent a condition related to RSV. Therefore, a use of an isolated, synthetic or recombinant antibody or a functional, derivative and / or analogous part thereof or a nucleic acid sequence or functional equivalent thereof or vector or cell according to the invention for the invention is also provided. preparation of a medicament and / or prophylactic agent to at least partly treat and / or prevent a condition related to RSV, as well as a method to at least partly treat or prevent a condition related to RSV, the method comprises administering to an individual in need thereof a therapeutically effective amount of an isolated, synthetic or recombinant antibody or a functional, derivative and / or analogous part thereof according to the invention. In a preferred embodiment, a combination with at least one other RSV specific agent is used, preferably another RSV specific antibody. Said individual has preferably been diagnosed as infected by RSV before treatment.
Dicho anticuerpo preferiblemente comprende el anticuerpo AM22, o una parte funcional del mismo. Dicho al menos otro anticuerpo específico al RSV preferiblemente es el palivizumab, D25, AM14, AM16 o AM23. Más preferiblemente se utiliza una combinación de AM22 y D25. Said antibody preferably comprises the AM22 antibody, or a functional part thereof. Said at least one other RSV specific antibody is preferably palivizumab, D25, AM14, AM16 or AM23. More preferably a combination of AM22 and D25 is used.
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Claims (1)
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| CA2633157C (en) | 2005-12-09 | 2018-10-09 | Academisch Medisch Centrum Bij De Universiteit Van Amsterdam | Means and methods for influencing the stability of antibody producing cells |
| WO2007067032A1 (en) | 2005-12-09 | 2007-06-14 | Academisch Medisch Cemtrum Bij De Universiteit Van Amsterdam | Means and methods for influencing the stability of cells |
| JP5624276B2 (en) | 2006-03-31 | 2014-11-12 | 中外製薬株式会社 | Methods for controlling blood kinetics of antibodies |
| EP1997830A1 (en) | 2007-06-01 | 2008-12-03 | AIMM Therapeutics B.V. | RSV specific binding molecules and means for producing them |
| JP5334319B2 (en) | 2007-09-26 | 2013-11-06 | 中外製薬株式会社 | Method for modifying isoelectric point of antibody by amino acid substitution of CDR |
| KR20220162801A (en) | 2008-04-11 | 2022-12-08 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
| EP2454283B1 (en) | 2009-07-15 | 2018-03-14 | AIMM Therapeutics B.V. | Means and methods for producing high affinity antibodies |
| US8568726B2 (en) | 2009-10-06 | 2013-10-29 | Medimmune Limited | RSV specific binding molecule |
| EP2647706B1 (en) | 2010-11-30 | 2023-05-17 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
| NZ611600A (en) * | 2010-12-02 | 2015-02-27 | Aimm Therapeutics Bv | Means and methods for producing high affinity antibodies |
| EP2679681B2 (en) | 2011-02-25 | 2023-11-15 | Chugai Seiyaku Kabushiki Kaisha | FcgammaRIIB-specific FC antibody |
| TW201817744A (en) | 2011-09-30 | 2018-05-16 | 日商中外製藥股份有限公司 | Therapeutic antigen-binding molecule with a FcRn-binding domain that promotes antigen clearance |
| WO2013047748A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule promoting disappearance of antigens having plurality of biological activities |
| WO2013095091A2 (en) | 2011-11-17 | 2013-06-27 | Aimm Therapeutics B.V. | Rsv g protein specific antibodies |
| WO2013081143A1 (en) | 2011-11-30 | 2013-06-06 | 中外製薬株式会社 | Drug containing carrier into cell for forming immune complex |
| BR112015001955A2 (en) | 2012-08-24 | 2017-11-07 | Chugai Pharmaceutical Co Ltd | fcgamariib specific fc region variant |
| PL2950886T3 (en) | 2013-02-01 | 2020-06-01 | Medimmune, Llc | Respiratory syncytial virus f protein epitopes |
| RU2761631C2 (en) | 2013-03-13 | 2021-12-13 | Дзе Юнайтед Стэйтс Оф Америка, Эс Репрезентед Бай Дзе Секретэри, Департмент Оф Хелт Энд Хьюман Сервисиз | Rsv proteins in pre-confluence conformation and use thereof |
| US9738689B2 (en) | 2013-03-13 | 2017-08-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Prefusion RSV F proteins and their use |
| AU2014231357B2 (en) * | 2013-03-15 | 2018-06-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Epitope of RSV fusion protein and antibody identifying same |
| WO2014163101A1 (en) | 2013-04-02 | 2014-10-09 | 中外製薬株式会社 | Fc region variant |
| EP3741390A1 (en) | 2014-01-15 | 2020-11-25 | Medlmmune, LLC | Rsv-specific antibodies and functional parts thereof |
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| AU2005214988A1 (en) * | 2004-02-17 | 2005-09-01 | Absalus, Inc. | Super-humanized antibodies against respiratory syncytial virus |
| EP1997830A1 (en) * | 2007-06-01 | 2008-12-03 | AIMM Therapeutics B.V. | RSV specific binding molecules and means for producing them |
| MX2010002044A (en) * | 2007-09-07 | 2010-03-18 | Symphogen As | Methods for recombinant manufacturing of anti-rsv antibodies. |
| WO2009114815A1 (en) * | 2008-03-13 | 2009-09-17 | Dyax Corp | Libraries of genetic packages comprising novel hc cdr3 designs |
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